Selective delipidation of Mycobacterium bovis BCG retains antitumor efficacy against non-muscle invasive bladder cancer.

PURPOSE: Repeated instillations of bacillus Calmette et Guérin (BCG) are the gold standard immunotherapeutic treatment for reducing recurrence for patients with high-grade papillary non-muscle invasive bladder cancer (NMIBC) and for eradicating bladder carcinoma-in situ. Unfortunately, some patients are unable to tolerate BCG due to treatment-associated toxicity and bladder removal is sometimes performed for BCG-intolerance. Prior studies suggest that selectively delipidated BCG (dBCG) improves tolerability of intrapulmonary delivery reducing tissue damage and increasing efficacy in preventing Mycobacterium tuberculosis infection in mice. To address the lack of treatment options for NMIBC with BCG-intolerance, we examined if selective delipidation would compromise BCG's antitumor efficacy and at the same time increase tolerability to the treatment. MATERIALS AND METHODS: Murine syngeneic MB49 bladder cancer models and in vitro human innate effector cell cytotoxicity assays were used to evaluate efficacy and immune impact of selective delipidation in Tokyo and TICE BCG strains. RESULTS: Both dBCG-Tokyo and dBCG-TICE effectively treated subcutaneous MB49 tumors in mice and enhanced tumor-infiltrating CD8+ T and natural killer cells, similar to conventional BCG. However, when compared to conventional BCG, only dBCG-Tokyo retained a significant effect on intratumoral tumor-specific CD8+ and γδ T cells by increasing their frequencies in tumor tissue and their production of antitumoral function-related cytokines, i.e., IFN-γ and granzyme B. Further, dBCG-Tokyo but not dBCG-TICE enhanced the function and cytotoxicity of innate effector cells against human bladder cancer T24 in vitro. CONCLUSIONS: These data support clinical investigation of dBCG-Tokyo as a treatment for patients with BCG-intolerant NMIBC.

The relationship between culture-related grief beliefs, prolonged grief disorder and suicide ideation among Shidu parents in rural China.

BACKGROUND: There are many one-child families in China due to the one-child policy. Parents who have lost their only child and are unable to conceive another child or unwilling to adopt a child are called Shidu parents in China. The death of an only child puts Shidu parents at the risk of mental illness and even suicide. Few studies have explored the influence of cultural beliefs and prolonged grief disorder on suicide ideation. METHODS: This study involved rural Shidu parents from Sujiatun district of Shenyang, China. Questionnaires consisted of the Prolonged Grief questionnaire - 13 (PG-13), the Culture-related Grief Beliefs of Shidu Parents Questionnaire (CBSQ), one question from the baseline National Comorbidity Survey (NCS) to measure suicide ideation and demographic and bereavement-related information. Bivariate logistic regression analyses were conducted to explore associated factors of suicide ideation. RESULTS: Sixty-nine (28.8%) of the 240 Shidu parents reported having suicide ideation. Having chronic disease (OR = 5.509, p < 0.01), having religious belief (OR = 3.923, p < 0.05) and having a grandchild (OR = 2.552, p < 0.05) were associated with an increased risk of suicide ideation. Destiny belief (a subscale of CBSQ) was negatively associated with suicide ideation (OR = 0.818, p < 0.05). Prolonged grief disorder (OR = 9.280, p < 0.01) and perceived stigma (a subscale of CBSQ) (OR = 1.200, p < 0.05) was positively associated with suicide ideation after adjusting for controlling variables. CONCLUSIONS: Suicide ideation is prevalent in rural Shidu parents. Reducing perceived stigma and alleviating prolonged grief disorder may decrease the risk of suicide among rural Shidu parents.

Mobile phone addiction and depression among Chinese medical students: the mediating role of sleep quality and the moderating role of peer relationships.

The literature has shown that mobile phone addiction is an important risk factor for depression. However, the internal mechanisms of mobile phone addiction leading to depression are still not clear. This study examined the mediating role of sleep quality and moderating role of peer relationships in the association between mobile phone addiction and depression. A sample of 450 Chinese medical students were recruited to complete measures of mobile phone addiction, depression, sleep quality and peer relationships. In this study, SPSS 25.0 and macro PROCESS were used to conduct statistical analysis on the collected data. The results showed that sleep quality partially mediated the association between mobile phone addiction and depression. Moreover, the effect of sleep quality on depression was moderated by peer relationships. The present study can advance our understanding of how and when mobile phone addiction leads to depression. Limitations and implications of this study are discussed.

A comparison of survival outcomes and side effects of toremifene or tamoxifen therapy in premenopausal estrogen and progesterone receptor positive breast cancer patients: a retrospective cohort study.

BACKGROUND: In premenopausal women, endocrine adjuvant therapy for breast cancer primarily consists of tamoxifen alone or with ovarian suppressive strategies. Toremifene is a chlorinated derivative of tamoxifen, but with a superior risk-benefit profile. In this retrospective study, we sought to establish the role of toremifene as an endocrine therapy for premenopausal patients with estrogen and/or progesterone receptor positive breast cancer besides tamoxifen. METHODS: Patients with early invasive breast cancer were selected from the breast tumor registries at the Sun Yat-Sen Memorial Hospital (China). Premenopausal patients with endocrine responsive breast cancer who underwent standard therapy and adjuvant therapy with toremifene or tamoxifen were considered eligible. Patients with breast sarcoma, carcinosarcoma, concurrent contralateral primary breast cancer, or with distant metastases at diagnosis, or those who had not undergone surgery and endocrine therapy were ineligible. Overall survival and recurrence-free survival were the primary outcomes measured. Toxicity data was also collected and compared between the two groups. RESULTS: Of the 810 patients reviewed, 452 patients were analyzed in the study: 240 received tamoxifen and 212 received toremifene. The median and mean follow up times were 50.8 and 57.3 months, respectively. Toremifene and tamoxifen yielded similar overall survival values, with 5-year overall survival rates of 100% and 98.4%, respectively (p = 0.087). However, recurrence-free survival was significantly better in the toremifene group than in the tamoxifen group (p = 0.022). Multivariate analysis showed that recurrence-free survival improved independently with toremifene (HR = 0.385, 95% CI = 0.154-0.961; p = 0.041). Toxicity was similar in the two treatment groups with no women experiencing severe complications, other than hot flashes, which was more frequent in the toremifene patients (p = 0.049). No patients developed endometrial cancer. CONCLUSION: Toremifene may be a valid and safe alternative to tamoxifen in premenopausal women with endocrine-responsive breast cancer.

Transcriptomic Profiling of Breast Cancer Cells Induced by Tumor-Associated Macrophages Generates a Robust Prognostic Gene Signature.

Breast cancer, one of the most prevalent neoplasms in the world, continues attracting worldwide attention. Macrophage, as the most abundant non-malignant cell in tumor, plays critical roles in both immune surveillance and tumorigenesis and has become a cell target of immunotherapy. Among all macrophages, tumor-associated macrophage (TAM) is regarded as the main force to promote tumorigenesis. To get an overall view of its impact on breast cancer, we employed a simplified and indirect coculturing cell model followed by RNA-sequencing to detect cancer cell's transcriptomic response induced by TAM and a prognostic gene signature was constructed based on it. Evidence from both cell models and clinical samples strengthened TAM's full-dimensional impact on breast cancer, involved in almost all known signal pathways dysregulated during tumorigenesis from transcription, translation and molecule transport to immune-related pathways. Consequently, the gene signature developed from these genes was tested to be powerful in prognostic prediction and associated with various clinical and biological features of breast cancer. Our study presented a more complete view of TAM's impact on breast cancer, which strengthened its role as an important therapy target. A 45-gene signature from the TAM-regulated genes was developed and shown potential in clinical application.

Predictors of prolonged grief disorder in Chinese elderly shidu parents: The role of perceived stigma and perceived stress.

INTRODUCTION: Parents who have lost their only child and over the age of 60 are known as elderly shidu parents. This study aimed to investigate predictors of prolonged grief disorder (PGD) among Chinese elderly shidu parents. METHODS: Two hundred and ninety-eight elderly shidu parents from Shenyang were included in this cross-sectional study. Participants completed a questionnaire including the Prolonged Grief questionnaire-13 (PG-13), the PTSD (post-traumatic stress disorder) Checklist for DSM-5 (PCL-5), the Center for Epidemiologic Studies Depression Scales (CES-D), the Self-Rating Anxiety Scale (SAS), and the Perceived Stress Scale-10 (PSS-10). Multiple linear regression was used to examine socio-demographic, bereavement-related and perceived stress associated with PGD symptoms. RESULTS: The prevalence of PGD among Chinese elderly shidu parents was 13.8%. Among the 41 PGD patients, 29, 39, 36 patients had comorbidity of PTSD, depressive symptoms and anxiety, respectively. Perceived stress, higher educational level, lower annual household income, perceived stigma, violent death of the child, and being in debt were associated with severer PGD symptoms. DISCUSSION: The present study revealed the prevalence of PGD and the important role of PGD in diagnosing other mental disorders in Chinese elderly shidu parents. Providing financial help, eliminating social stigma, and stress should be included in PGD prevention among Chinese elderly shidu parents.

A single-center, prospective and randomized controlled study: Can the prophylactic use of lamivudine prevent hepatitis B virus reactivation in hepatitis B s-antigen seropositive breast cancer patients during chemotherapy?

Over the past four decades, chemotherapy has played an important role in prolonging survival in breast cancer patients. However, it may also result in undesirable side effects such as hepatitis B virus (HBV) reactivation seen in this study. With the increasing use of chemotherapy paralleling the rise in breast cancer incidence, the occurrence of HBV reactivation is likely to further increase. Several strategies use lamivudine to deal with this problem. Initially, lamivudine had been used to treat patients who developed alanine transaminase elevation attributable to HBV reactivation during chemotherapy. However, using this strategy, fatal reactivation has also been reported. Later studies have suggested that prophylactic lamivudine significantly reduces HBV reactivation and its associated morbidity. However, these studies were based mainly on patients with lymphoma, whereas studies on breast cancer patients were few. Moreover, these studies were retrospective. Recently, a prospective study has recommended that deferred preemptive lamivudine could be a comparable alternative to the prophylactic strategy. However, it was not a randomized controlled study. In this study, it was examined the efficacy of the prophylactic strategy in hepatitis B s-antigen seropositive breast cancer patients during chemotherapy using a prospective, randomized controlled study. Two groups were studied. One group consisted of 21 patients who were treated with prophylactic lamivudine, the other group consisted of 21 patients who were not treated with prophylactic lamivudine. The results showed that the prophylactic lamivudine strategy significantly decreased the incidence of HBV reactivation (0 vs. 28.6%, P = 0.021). It was conclude that the prophylactic lamivudine strategy significantly reduces the incidence of HBV reactivation for hepatitis B s-antigen seropositive breast cancer undergoing chemotherapy.

Culture-related grief beliefs and social support influence depressive symptoms of Shidu parents in rural China.

Background: Parents who have lost their only child are known as Shidu parents in China. Losing an only child is an enormous tragedy for parents that can trigger severe depressive symptoms. Few studies have explored the influence of cultural beliefs and social support on depressive symptoms. Objective: This study aimed to explore the relationship between culture-related grief beliefs, social support and depressive symptoms among Shidu parents in rural China. Method: This cross-sectional study was conducted in Sujiatun district of Shenyang, China. Data were collected from November 2019 to February 2020 from 228 rural Shidu parents. Questionnaires consisted of the Center for Epidemiologic Studies Depression Scales (CES-D), the Culture-related Grief Beliefs of Shidu Parents Questionnaire (CBSQ), the Social Support Rating Scale (SSRS), and demographic and bereavement-related information. Hierarchical multiple linear regression analysis was conducted to examine the associations among culture-related grief beliefs, social support and depressive symptoms. Results: Of the 228 Shidu parents, 87.0% reported depressive symptoms (CES-D ≥ 16). The mean age of the participants was 62.91 years, ranging from 50 to 86. Regression analysis indicated that parents' younger age, lower education level and debts were prominent risk factors for depressive symptoms. Perceived stigma (a subscale of CBSQ) was positively associated with depressive symptoms. Social support was negatively associated with depressive symptoms. Conclusions: Given the high prevalence of depressive symptoms in rural Shidu parents, there is a critical need to reduce perceived stigma and increase social support to alleviate depressive symptoms among Shidu parents in rural China.

Antecedentes: Los padres que han perdido a su único hijo se conocen como padres Shidu en China. Perder un hijo único es una tragedia enorme para los padres que puede desencadenar síntomas depresivos graves. Pocos estudios han explorado la influencia de las creencias culturales y el apoyo social sobre los síntomas depresivos.Objetivo: Este estudio tuvo como objetivo explorar la relación entre las creencias de duelo relacionadas con la cultura, el apoyo social y los síntomas depresivos en padres Shidu de las zonas rurales de China.Método: Este estudio transversal se realizó en el distrito Sujiatun de Shenyang, China. Los datos se recopilaron desde noviembre de 2019 hasta febrero de 2020 en 228 padres Shidu rurales. Los cuestionarios consistieron en las Escalas de Depresión del Centro de Estudios Epidemiológicos (CES-D por su sigla en inglés), el Cuestionario de Creencias de Duelo relacionadas con la Cultura de los Padres Shidu (CBSQ por su sigla en inglés), la Escala de Calificación de Apoyo Social (SSRS por su sigla en inglés) e información demográfica y relacionada con el duelo. Se realizó un análisis de regresión lineal multiple jerárquica para examinar las asociaciones entre las creencias de duelo relacionadas con la cultura, el apoyo social y los síntomas depresivos.Resultados: De los 228 padres Shidu, el 87% reportó síntomas depresivos (CES-D ≥ 16). La edad media de los participantes fue de 62,91 años, con un rango de 50 a 86. El análisis de regresión indicó que la edad más joven de los padres, un nivel educativo más bajo y las deudas eran factores de riesgo importantes para los síntomas depresivos. El estigma percibido (una subescala del CBSQ) se asoció positivamente con síntomas depresivos. El apoyo social se asoció negativamente con síntomas depresivos.Conclusiones: Dada la alta prevalencia de síntomas depresivos en los padres Shidu rurales, existe una necesidad crítica de reducir el estigma percibido y aumentar el apoyo social para aliviar los síntomas depresivos entre los padres Shidu en las zonas rurales de China.

Variation of soil nutrients and bacterial community diversity of different land utilization types in Yangtze River Basin, Chongqing Municipality.

The diversity and community distribution of soil bacteria in different land use types in Yangtze River Basin, Chongqing Municipality were studied by using Illumina MiSeq analysis methods. Soil physical and chemical properties were determined, and correlation analyses were performed to identify the key factors affecting bacterial numbers and α-diversity in these soils. The results showed that the soil physical and chemical properties of different land use types decrease in the order: mixed forest (M2) > pure forest (P1) > grassland (G3) > bare land (B4). There were significant differences in bacterial diversity and communities of different land use types. The diversity of different land use types showed the same sequence with the soil physical and chemical properties. The abundance and diversity of bacterial in M2 and P1 soils was significantly higher than that in G3 and B4 soils. At phylum level, G3 and B4 soils were rich in only Proteobacteria and Actinobacteria, whereas M2 and P1 soils were rich in Proteobacteria, Actinobacteria and Firmicutes. At genus level, Faecalibacterium and Agathobacter were the most abundant populations in M2 soil and were not found in other soils. Pearson correlation analysis showed that soil moisture content, pH, AN, AP, AK and soil enzyme activity were significantly related to bacterial numbers, diversity and community distribution.

Oncogene PRR14 promotes breast cancer through activation of PI3K signal pathway and inhibition of CHEK2 pathway.

Nuclear envelope component PRR14 has been detected to be upregulated in varieties of cancers, especially in breast cancer. But its role in breast carcinogenesis is poorly understood. In this study, we show PRR14 contributes to breast carcinogenesis mainly through overexpression, which derives from elevated transcription and gene amplification. Increased PRR14 expression promotes breast cancer cell proliferation and tumor formation. Biochemical analysis reveals, in addition to previously reported activation of PI3-kinase/Akt/mTOR pathway, PRR14 overexpression regulates cell cycle in breast cancer by inhibiting CHEK2's activation, followed with the deregulation of DNA damage pathway. In correspondence, CHEK2 and PRR14 show opposite impact on breast cancer patients receiving chemotherapy. Collectively, our study is the first to document the oncogenetic role of PRR14 in breast cancer, which protects cells from apoptosis and stimulates proliferation by activating the PI3-kinase/Akt/mTOR pathway and inhibiting the CHEK2 pathway. Both of these pathways are of great influence in breast cancer and PRR14 appears to be their novel interacting node, which renders patients more resistance to chemotherapy and provides a potential therapeutic target in breast cancer.

Concomitant a giant pulmonary bulla on the left lower lobe and hamartoma successfully treated by video-assisted thoracoscopic pulmonary wedge resection.

A 48-year-old woman was admitted for pectoralgia and dyspnea. Tomography revealed a giant lung bulla with a mass arose from the bulla wall in the left lower lobes, and left lower lobes pulmonary wedge resection was performed through video-assisted thoracic surgery (VATS). The giant bulla was formed by fibrous connective tissue covered by monolayer pavement epithelium. The trabecular bone, cartilage and adipose tissue were found in the nodular lesion. The final diagnosis was giant pulmonary bulla with hamartoma, a very rare condition and previously unreported in the literature. Surgical approach for complete resection of the bulla was a curative treatment.

Targeting CCR2 with its antagonist suppresses viability, motility and invasion by downregulating MMP-9 expression in non-small cell lung cancer cells.

Non-small cell lung cancer (NSCLC) is the most common type of lung cancer, which is the leading cancer killer in the world. Despite the recent advances in its diagnosis and therapy, the prognosis of NSCLC patients remains very poor, mainly due to the development of drug resistance and metastasis. Both the chemokine network and the matrix metalloproteinase (MMP) system play important roles in cancer cell metastasis. The disruption of CCL2/CCR2 chemokine signaling has been shown to suppress cancer cellviability and metastasis. CCL2-neutralizing antibodies, which have shown promising therapeutic efficacy in several cancer models, are not widely used due to technical issues. CCR2 antagonism has thus become an alternative method for cancer treatment. However, the effect of CCR2 antagonists on NSCLC progression remains poorly understood. Here, we investigated the effect of CCR2 antagonist (CAS445479-97-0) on the proliferation, migration and invasion of human lung adenocarcinoma A549 cells by using WST-1 cell viability assay, transwell migration assay, wound healing scratch assay and Matrigel invasion assay. We demonstrated that CCL2 treatment promoted A549 cell viability, motility and invasion by upregulating MMP-9 expression and that this induction was significantly suppressed by CAS 445479-97-0. Taken together, our data suggested that the CCR2 antagonist would be a potential drug for treating CCR2-positive NSCLC patients.

Inhibition of breast cancer cell growth by the Pteris semipinnata extract ent-11α-hydroxy-15-oxo-kaur-16-en-19-oic-acid.

Previous studies have demonstrated strong anti-tumor effects of ent-11α-hydroxy-15-oxo-kaur-16-en-19-oic-acid (5F), an extract from Pteris semipinnata, in liver, lung, stomach and anaplastic thyroid cancer cells. However, whether 5F inhibits the growth of breast cancer cells remains unclear. The present study assessed the effect of 5F on breast cancer cells. The breast cancer cell lines MCF-7, MDA-MB-231 and SK-BR-3 were each treated with 0, 5, 10, 20 and 40 µg/ml 5F. Morphological changes in the breast cancer cells were assessed using fluorescence microscopy. The proliferation and apoptosis of the breast cancer cells were also examined using Cell Counting Kit-8 and flow cytometry. The levels of B-cell lymphoma 2 (Bcl-2), Bcl-2-associated X apoptosis regulator (Bax), Bcl-2 antagonist/killer (Bak) 1 and caspase-3 in the breast cancer cells were assessed. The results of the present study demonstrated that 5F inhibited the proliferation of MCF-7, MDA-MB-231 and SK-BR-3 breast cancer cells in a concentration- and time-dependent manner. Treatment with 5F also induced the apoptosis of breast cancer cells. MDA-MB-231, MCF-7, and SK-BR-3 cells exhibited apoptotic rates of 40.13, 60.44, and 70.49%, respectively, following incubation with 5F for 24 h. Furthermore, 5F significantly decreased the expression of Bcl-2 and increased the expression of Bax, Bak, and caspase-3 in a concentration-dependent manner. The results of the present study revealed that the P. semipinnata extract 5F inhibited the growth of human breast cancer cells in a time- and concentration-dependent manner, and that 5F induced apoptosis of human breast cancer cells.

Selenocystine-induced cell apoptosis and S-phase arrest inhibit human triple-negative breast cancer cell proliferation.

Triple-negative breast cancer (TNBC) is an aggressive subtype of breast cancer with limited effective treatment options. New therapeutic approaches are urgently needed to improve the prognosis of TNBC. Here we demonstrated that a redox modulator, selenocystine (SeC), significantly inhibits TNBC cell proliferation in a dose- and time-dependent manner. Through cell apoptosis assays and cell cycle distribution analyses, we have shown that the in vitro inhibitory effect of SeC on TNBC cells can be attributed to the induction of apoptosis and the S-phase arrest in a dose-dependent manner. Therefore, this finding implies that SeC potentially is a novel therapeutic agent for TNBC.